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Unusual staining of immunohistochemical markers PAX8 and CDX2 in breast carcinoma: a potential diagnostic pitfall

Knowing the sensitivity and specificity of tissue-specific immunohistochemical markers is crucial for accurate determination of the primary tumor site. PAX8 has been used as a diagnostic marker for carcinomas of the gynecologic tract, kidney, and thyroid gland, and CDX2 has been used as a marker of...

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Published in:Human pathology 2022-07, Vol.125, p.35-47
Main Authors: Shen, Tiansheng, Zhao, Jun, Zhao, Min, Taggart, Melissa W., Ramalingam, Preetha, Gong, Yun, Wu, Yun, Liu, Hui, Zhang, Jinxia, Resetkova, Erika, Wang, Wei-Lien, Ding, Qingqing, Huo, Lei, Yoon, Esther
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Language:English
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Summary:Knowing the sensitivity and specificity of tissue-specific immunohistochemical markers is crucial for accurate determination of the primary tumor site. PAX8 has been used as a diagnostic marker for carcinomas of the gynecologic tract, kidney, and thyroid gland, and CDX2 has been used as a marker of gastrointestinal carcinoma. Neither is considered a marker for breast carcinoma (BC). However, we have encountered BCs that express PAX8 or CDX2, some of which caused diagnostic confusion. We investigated the immunohistochemical staining frequency of PAX8 and CDX2 in BC. We identified 237 BCs for which PAX8 staining results were reported (102 primary and 135 metastatic BCs); seven primary and four metastatic BCs (4.6%) were positive for PAX8, with various intensities and staining patterns. CDX2 staining results were reported for 271 BCs (78 primary and 193 metastatic); four primary BCs and one metastatic BC (1.8%) were positive for CDX2, ranging from focal and weak to diffuse and strong. We also stained primary invasive BCs with PAX8 and CDX2 using tissue microarrays. None of the 332 PAX8-stained cases was positive, while one of 143 CDX2-stained cases was positive. Four PAX8-positive and three CDX2-positive cases were stained with TRPS1, and all were positive for TRPS1. In addition, we reviewed the literature for PAX8 and CDX2 expression in BCs and found 5.5% PAX8-positive BCs (90/1625) in 17 studies and 0.8% CDX-2 positive BCs (7/909) in 20 studies. PAX8 and CDX2 are infrequently expressed in BC by immunohistochemistry, and in rare cases, the staining can be strong and diffuse. Additional diagnostic markers are necessary and helpful in distinguishing breast from other primary origins. •PAX8 and CDX2 can be infrequently positive in breast carcinomas and can cause diagnostic pitfall in patients with prior oncologic history.•TRPS1 is a sensitive and specific marker to breast carcinoma.•Clinical history and a panel of markers including CK7, GATA3, and TRPS1 can help in coming to correct diagnosis.
ISSN:0046-8177
1532-8392
DOI:10.1016/j.humpath.2022.04.007